Real-time monitor solid phase peptide synthesis by mass spectrometry

Abstract

Provided are systems, apparatus, materials and methods for directly monitoring products and intermediates of solid phase chemical synthesis such as solid phase peptide synthesis.

What is claimed is: 
     
       1. A method for real-time monitoring of a chemical reaction using a mass spectrometer, said method comprising the steps of:
 a) providing a synthesized sample bonded to a solid phase synthesis support in/from a container where the chemical synthesis occurs; 
 b) subjecting the synthesized sample on a plate to an organic solvent; 
 c) using a light source to break the chemical bond directly between the sample and solid phase synthesis support to which it is attached and transport the analyte molecules in an electrospray ionization plume; and 
 d) analyzing the precursor ion spectrum of the analyte molecules to determine the molecular weight of synthesis products. 
 
     
     
       2. A method of  claim 1 , wherein the chemical reaction is peptide synthesis. 
     
     
       3. A method of  claim 2 , wherein the said peptide synthesis is solid phase peptide synthesis. 
     
     
       4. A method of  claim 1 , wherein the organic solvent is selected from dichloromethane or methanol. 
     
     
       5. A method of  claim 4 , wherein the organic solvent is selected from dichloromethane. 
     
     
       6. A method of  claim 1 , wherein the plate is selected from steel or polyester. 
     
     
       7. A method of  claim 6 , wherein the polyester is selected from polyethylene terephthalate. 
     
     
       8. A method of  claim 7 , wherein polyethylene terephthalate is black. 
     
     
       9. A method for real-time monitoring of solid phase peptide synthesis using a mass spectrometer, said method comprising the steps of:
 a) providing a peptide bonded directly to a solid phase peptide synthesis support in/from a container where the chemical synthesis occurs; 
 b) subjecting the synthesized peptide on a plate to an organic solvent; 
 c) using a light source to break the chemical bond directly between the sample and solid phase peptide synthesis support to which it is attached and transport the analyte molecules in an electrospray ionization plume; and 
 d) analyzing the precursor ion spectrum of the analyte molecules to determine the molecular weight of synthesis products. 
 
     
     
       10. A method of  claim 9 , wherein the organic solvent is selected from dichloromethane. 
     
     
       11. A method of  claim 9 , wherein the plate is selected from steel or polyester. 
     
     
       12. A method of  claim 11 , wherein the polyester is selected from polyethylene terephthalate. 
     
     
       13. A method of  claim 12 , wherein the polyethylene terephthalate is black. 
     
     
       14. A method of  claim 1 , wherein the real-time monitoring of a chemical reaction is performed in a system comprising:
 a) a sample; 
 b) a solvent exchange reservoir; 
 c) a light source; 
 d) an electrospray unit, and 
 e) a mass spectrometer. 
 
     
     
       15. A method of  claim 14 , wherein the said sample is in/from a chemical synthesis reactor. 
     
     
       16. A method of  claim 15 , wherein the said chemical synthesis is peptide synthesis. 
     
     
       17. A method of  claim 16 , wherein said peptide synthesis is solid phase peptide synthesis.